Skip to Main content Skip to Navigation
Journal articles

Impact of hepatitis C virus and alcohol, alone and combined, on the unfolded protein response in primary human hepatocytes

Abstract : Hepatitis C virus (HCV) infection and alcohol abuse are leading causes of chronic liver disease and frequently coexist in patients. The unfolded protein response (UPR), a cellular stress response ranging along a spectrum from cytoprotection to apoptosis commitment, has emerged as a major contributor to human diseases including liver injuries. However, the literature contains conflicting reports as to whether HCV and ethanol activate the UPR and which UPR genes are involved. Here we have used primary human hepatocytes (PHH) to reassess this issue and address combined impacts. In this physiologically relevant model, either stressor activated a chronic complete UPR. However, the levels of UPR gene induction were only modest in the case of HCV infection. Moreover, when combined to the strong stressor thapsigargin, ethanol exacerbated the activation of pro-apoptotic genes whereas HCV tended to limit the induction of key UPR genes. The UPR resulting from HCV plus ethanol was comparable to that induced by ethanol alone with the notable exception of three pro-survival genes the expressions of which were selectively enhanced by HCV. Interestingly, HCV genome replication was maintained at similar levels in PHH exposed to ethanol. In conclusion, while both HCV and alcohol activate the hepatocellular UPR, only HCV manipulates UPR signalling in the direction of a cytoprotective response, which appears as a viral strategy to spare its own replication.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03488713
Contributor : Accord Elsevier CCSD Connect in order to contact the contributor
Submitted on : Thursday, July 21, 2022 - 9:29:56 AM
Last modification on : Friday, August 5, 2022 - 11:57:55 AM

File

S0300908419303074.pdf
Files produced by the author(s)

Licence


Distributed under a Creative Commons Attribution - NonCommercial 4.0 International License

Identifiers

Citation

Céline Hernandez, Etienne B. Blanc, Véronique Pène, Béatrice Le-Grand, Maxime Villaret, et al.. Impact of hepatitis C virus and alcohol, alone and combined, on the unfolded protein response in primary human hepatocytes. Biochimie, 2020, 168, pp.17 - 27. ⟨10.1016/j.biochi.2019.10.012⟩. ⟨hal-03488713⟩

Share

Metrics

Record views

21

Files downloads

0